The B lymphocytes, or B-cells, of the immune system of vertebrate animals provide an antibody response to a foreign antigen introduced into the body of the animal. In birds, precursor B-cells are differentiated in an organ called the bursa of Fabricius. In mammals, no equivalent organ to the bursa of Fabricius has been discovered and it has been considered that hematopoietic precursors to B-cells are present and may differentiate into mature B-cells within the bone marrow.
Until recently the hormonal inducer of the differentiation of B-cell precursors into B-cells has been unknown. However, in earlier studies by one of the present inventors and others, the existence of a specific B-cell differentiating inducer was demonstrated in the extracts of the bursa of Fabricius from chickens. This early work is reported in the following articles, which are incorporated herein by reference: Brand, et al, Science, 193:319-321 (July 23, 1976); Brand, et al, Nature, 269:597-598 (Oct. 13, 1977); Goldstein, et al, Cold Spring Harbor Symposia on Quantitative Biology, XLI:5-8 (1977); and Goldstein, in "Molecular Control of Proliferation and Differentiation", pgs. 197-202, Academic Press (1977).
More recently, the present inventors and others identified a tripeptide hormone called bursin, which has the amino acid sequence Lys-His-Gly-NH.sub.2, as a specific inducer of B-cell differentiation. This peptide, also known as bursopoietin, is active in both birds and mammals and is described in U. S. Pat. No. 4,584,284 which is incorporated herein by reference.
Other endocrine peptides have been disclosed in the art. Somatostatin is a cyclic tetra-decapeptide produced by the hypothalamus and cells of the Islets of Langerhans. Somatostatin inhibits the release of a variety of hormones such as somatotropin, thyrotropin, corticotropin, insulin, glucagon, gastrin, secretin and renin. Another such regulating peptide is tuftsin, a basic tetrapeptide produced from circulating immunoglobulin, that stimulates phagocytosis in polymorphonuclear leucocytes and in macrophages. [See, e.g., V. A. Najjar et al, Nature, 228:672 (1970); A. Constantopoulos et al, Cytobios., 6:97 (1972); and Y. Stabinsky et al, Mol. Cell. Biochem., 30:71 (1980)].
The interrelationship of these hormones, including the B-cell differentiation factor bursin, has yet to be elucidated. The discovery of the association of a variety of hormones active in differentiating B-cells and providing effects on other tissues offers the potential for new treatments of immune disorders and liver dysfunction in humans and animals.